The goal is to demonstrate prospectively whether or not the course of microvascular complications in insulin-dependent diabetes mellitus can be modified by altered glycemic control. The major question addressed is whether significantly different mean levels of glycemia can be maintained in comparable groups of volunteers with IDDM and whether these will be associated with different rates of evolution of microangiopathy. The feasibility of recruitment and randomization of volunteers to standard and experimental treatments as defined, and of attainment of different target levels of glycemic control in two groups, was demonstrated with participation of this clinic, through periods of more than 1 year in phase II of the study. It is proposed that patients will continue to be recruited according to the specified eligibility criteria. After giving informed consent volunteers will be randomized to the standard treatment with one or two injections of insulin a day, or to an experimental treatment based on multiple daily infections or continuous subcutaneous infusion of insulin. Glycemic control will be assessed according to measurements of blood glucose and hemoglobin A1C. The protocol incorporates safeguards against the risks of the treatments and has been judged ethically acceptable. During phases I and II of the study the University of Western Ontario (UWO, Clinic 18) has developed the staff and facilities required for phase III. Strategies for ensuring successful recruitment, for maintenance of adherence to the protocol, and for recognition and minimization of intercurrent events, are outlined. The summation of data from all DCCT clinics will be used to test the question whether the attainable relative improvement in glycemic control resulting from the experimental treatment as defined can prevent or ameliorate microvascular complications of Type I diabetes.